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      Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.

      Nature medicine

      Animals, Benzamides, Blood Cells, drug effects, Bone Marrow, Dose-Response Relationship, Drug, Enzyme Inhibitors, pharmacology, Evaluation Studies as Topic, Fusion Proteins, bcr-abl, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, drug therapy, Mice, Piperazines, Protein-Tyrosine Kinases, antagonists & inhibitors, Proto-Oncogene Proteins c-abl, Pyrimidines, Stem Cells, Tumor Cells, Cultured

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          Abstract

          The bcr-abl oncogene, present in 95% of patients with chronic myelogenous leukemia (CML), has been implicated as the cause of this disease. A compound, designed to inhibit the Abl protein tyrosine kinase, was evaluated for its effects on cells containing the Bcr-Abl fusion protein. Cellular proliferation and tumor formation by Bcr-Abl-expressing cells were specifically inhibited by this compound. In colony-forming assays of peripheral blood or bone marrow from patients with CML, there was a 92-98% decrease in the number of bcr-abl colonies formed but no inhibition of normal colony formation. This compound may be useful in the treatment of bcr-abl-positive leukemias.

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          8616716

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